Multi-omics-based Label-free Metabolic Flux Inference Reveals Obesity-associated Dysregulatory Mechanisms in Liver Glucose Metabolism

Overview

Journal iScience

Publisher Cell Press

Date 2022 Mar 4

PMID 35243212

Authors

Saori Uematsu

Satoshi Ohno

Kaori Y Tanaka

Atsushi Hatano

Toshiya Kokaji

Yuki Ito

Hiroyuki Kubota

Ken-Ichi Hironaka

Yutaka Suzuki

Masaki Matsumoto

Keiichi I Nakayama

Akiyoshi Hirayama

Tomoyoshi Soga

Shinya Kuroda

Affiliations

Soon will be listed here.

Abstract

Glucose homeostasis is maintained by modulation of metabolic flux. Enzymes and metabolites regulate the involved metabolic pathways. Dysregulation of glucose homeostasis is a pathological event in obesity. Analyzing metabolic pathways and the mechanisms contributing to obesity-associated dysregulation is challenging. Here, we introduce OMELET: Omics-Based Metabolic Flux Estimation without Labeling for Extended -omic Analysis. OMELET uses metabolomic, proteomic, and transcriptomic data to identify relative changes in metabolic flux, and to calculate contributions of metabolites, enzymes, and transcripts to the changes in metabolic flux. By evaluating the livers of fasting / mice, we found that increased metabolic flux through gluconeogenesis resulted primarily from increased transcripts, whereas that through the pyruvate cycle resulted from both increased transcripts and changes in substrates of metabolic enzymes. With OMELET, we identified mechanisms underlying the obesity-associated dysregulation of metabolic flux in the liver.

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